Pyrrocoline polymethinecyanine dyes



Patented June 13, 1950 PYRROCOLINE POLYMETHINEGYANINE DYES Robert H. Sprague-and Leslie G. S. ,Brooker, Rochester N. Y., assignors to Eastman Kodak Company, Rochester, N. Y., a corpioration of New J ersey summing; Application Oc'toberl, 940,

Serial No. 700,393 f7 Claims. (omen-24o invention. relates .to .pyrrocoline poly- "methinecyanine dyes and. to. a process, for. preparing thesame.

,In our copending application Serial No. 407,033,.filed August;1.5,.1941 (now United States Patent 2,409,612), we.have disclosed pyrroc'oline polymethinecyanine dyes which, are useful as light-screeningsubstances in photographic emulsions. Wehavefound that some of these pyrro- :coline polymethinev dyes, (especially the quinoline pyrrocoline dimethinecyanine dyes) .areof use ginslthe treatment. of particular kinds of worm infestations. It is, accordingly, an ,object of our invention to provide pyrrocoline polymethine- "cyanine dyes. 4 A further object'is to provide'la processdor' preparing these newsdye's. Other I objects will become apparent hereinafter. The new pyrrocoline polymethinecyanine dyes of our finvention can be represented by the following; general formula: I /Q\ B-2II= (L" L)n- 1=F]-(CH=CH)d- -C=6k x R1-ru -R| wherein R represents an alcohol radical, i. e. an alkyl'group, e. g. methyl, ethyLu-propyl, n-butyl,

-isobutyl, n-amyl, s-hydroxyethyl, p-ethox'yethyl,

p-metlioxyethyl, -'y-hydroxypropyl, etc., Lv represents 1a 'methine group, e. g. -:-CH -;-'-"C(CH3) -C(C1) ,-etc., n represent apositive integer of:' from 1-to 2, z represents'the I :non-metallicatoms necessary to complete a heterocyclidn-ucleus containing 5' to 6 atoms in the*-heterocyclic ring, e. g; a heterocyclic nucleus of the 'thiazole" series :(for I instance thiazole;4'-methylthiazole, 4-phenylthiazole, 4,5-

diphenylthiazolepetc.J, aheterocyclic nucleus of the benzothiazole series (for instance;- benzo'thi 1 azole, 5-chlorobenzothiazole, 6-chlorobenzothia- .zole, a 5-dimethylaminobenzothiazole, G-methoxybenzothiazole, fi-methylbenzothiazole, 5,- rnethylbenzothiazole, 5-br o1nobenzothiazole, 4 methoxybenzothiazole, 7-chlorobenzothiazole,-etc., a heterocyclic nucleus of the;naphthothi-azole series (for instance, a-.-naphthothiazole, p-naphthothiazole, etc), a heterocyclic nucleus of the selenae zole seriesifor instance, selenazole, 4-methy1- .selenazole,. l-phenylselenazole, etc.) a heterocyfclicunucleus of the benzoselenazole series I (for instance .benzoselenazole, 5-.-chlorobenzoselerra.-

zole, etc.), aheterocycl icnucleus of the3benzoxa- .molesseries, (e; .g.-,-ben zoxazole, 5-phenylbenzoxa- ;zole,- 5-chlorobenzoxazole, 5-methoxybenzonazole,

etc), a. heterocyclic'. nucleus .of the quinoline :series ,(fon. instance. quinoline, G-methoxyquinozllne, .-6 e .chloroquinoline,-v 3 -.ch1oroquinoline,-3

methylquinoline, 6 dimethylaminoquinoline;6 acetylaminoquinoline, 6 phenylquinoline, 8"- meithylquinoline; 7 methylquinoline, 5 methylquinoline,;8-phenylquinoline, etc), etc., d' represents a; positive integer of-from 2 to 3, Q rep resents the non-metallic atoms necessary tocomplete a pyridine nucleus, R1 and Rz-each representsa-hydrogen atom, analkyl group, ;e. g..methyl,. qr. anaryl group, .e.,g;.phenyl, p-bromophenyl, etc., and X represents an anion, e. g. chloride, bromide, iodide, methylsulfate, ethylsulfate, benzenesulfonate}.B-toluenesulfonate, acetate, propionate, perchlorate, thiocyanate, etc.

To obtain our new 'pyrrocoline polym'ethinecyanine dyes, we condense a cyclammonium quaternary salt selectedirom those represented by the following general formula:

p coon; whereimR, L, .n, xqandzfhavethe values (given @above, :with a. .pyrrocoline. selected kfrom' those represented bythe iollowing general formula; I

' no: -i-r v, Irv-t f +111 1 wherein 62, R1 and R2 have-the values, given rbove. The condensations are efiected. in the presence of substantially anhydrous acetic acid,

e. g:'glacial acetic acid In acetic anhydride; the condensations do not take place. In contrast, it is to be noted that a-IIlGthYlindOlB condenses with cyclammonium quaternary salts such as those of Formula IItabovej in acetic anhydride. f

The following examples will serve toillustrate furtherthe manner of obtaining our new dyes.

Example 1se n? ethyl-2i-benzoraeole).(Zmlpenylcan; I f 1'.93fg. (1'mol.) 2-phenylpyrrocoline, 4.34 g. 1 mol.) 2-;3-acetanilidovinyl benzoxazole ethiodide and 25 cc.. .glacial acetic acid were refluxedlO minutes. Red coloration. Chilled, filtered; wash ed, with acetone and water and dried. Yield. of

red crystals 4.45 g., 91 per cent. After recrystallization fromabsolute ethyl alcohol, (19' c c1/ g5) the product was obtained as granular red crystals melting with decomposition at 204-205 C. Yield 3.9 g., 7}} per cent. Methyl alcohol solution orange. j i '5! J Example 2.(3-ethyl-2-benzo.razolel (z -methyl- 1 myrrocoline) di-methinecyanine iodide 4.34 g. (1 mol.) 2-p-acetanilidovinylloelfizoxa zole ethiodide, 1.3 g. (1 mol.) 2-methylpyrrocoline and cc. glacial acetic acid were refluxed, 1

Example 3.(3-ethyl 2 benzomazole) (2,3: di-

fmethyl 1 iodide pyrrocoline) c li1i1.eth.z"necyani'ne azole ethiodide, 1.5 g. (111101.) 2,3-dimethylpyrroooline and 25 cc. glacial acetic acid were refluxed 5 minutes. Red coloration. Chilled, stirred until crystalline, again chilled and filtered. Washed with acetone and water, and dried. Yield of dark red crystals 3.85 g1, 87 per cent. After 1 recrystallization from methyl alcohol (42 cc./g.)

the :dye was obtained as greenish-red needles with r green-reflex melting with decomposition at 266-267 0. Yield 3.55 g., 80 percent. Methyl alcohol solution orange. I

Example 4.3-ethyl-2-benzothiazole) (Z-p hen IZ- 1 -pyrrocoline) -tetramethinecyanine chloride C2415 CI 4.8 grams (1 mol.) 2-( l-acetanilido-lfi butadienyD-benzothiazole ethiodide, 1.93 grams (1 mol.) Z-phenyl-pyrrocoline and 30 cc. glacial acetic acid were refluxed 3 minutes. Blue coloration and green crystals of dye separated at once from the boiling mixture. washed with acetone and water and dried. Yield 2.6 grams, 49 per cent. The product was extracted with 700 cc. boiling methyl alcohol. Residue of green crystals 1.3 grams, M. P. 257-259 C. -The solution was chilled and yielded. .65 grams green-needles, M. P- 257-259 C. side by side with above. Combined yield 37 per cent. The dye was converted to chloride in 50 cc. cresol Chilled, filtered,

solution using 100 per centexcess freshly precipitated silver chloride. mechanically for 15 minutes at 100'C., filtered The mixture was stirred acidwere refluxed 5 minutes.

hot and chilled. Diluted to 400 cc. with ether and chilled overnight. The green crystals which separated were filtered ofi. washed with ether and acetone and dried'l? Yield 1'.6' gram s, 36 per cent. After recrystallization from absolute ethyl alcohol, (15 cc./g.) the product was obtained as green needles with bronze reflex melting at -86 6., yield 1.3 grams, 30 per cent. i Methyl alcohol solution bluish-red.

. Example 5.(3 -ethyZ-2-benzoacazole) (Z-methyl- 0 (I o-on on oj N/ I.

- l pyr rocoline)-tetramethinecyanine iodide T416. gran-s5 1 'ino 1. 2 (eacetaniiid netut dienyl) -benzoxazole ethiodide; 1,3 grams (1 mol.) Z-methyl-pyrrocoline and 30 cc. glacial acetic Blue coloration. Green crystals separated at once from the boilingmixture. Yield 2.9, rams, 64 per cent. Dis solved in 50 cc. cresol (m and p mixture) heated to C., filtered hot, cooled and diluted ,with 250 cc. methyl alcohol. Greencrys tals separated on chilling. Filtered, washed with methyl alcohol and dried. Yield 1.95 grams, 43 percent, M. P. 247-7250 C- with decomposition.v Methyl alcohol solution blue. g Example 6.(3-ethyl-2 benzothzazole) (2,3 dimethyl-I-pyrrocoline) -tetramethinecyanine ptoluenesulfonate which separated was'filtered off, washedwith ether, acetone and water and dried. Yield of green crystals, 2,3 grams, 43 per cent. After recrystallization frommethyl alcohol (32 cc./g.') the product was obtained as bright green crystalsmelting with decomposition at '2'72-273 C.

Yield 2.0 g., 38 per cent.

alcohol.

Erample 7.-(1,6-dimethyl-2-qui11;oline) (2 plien; yl-I -pyrrocoline) -dimethinecyanine chloride Solution blue in methyl I I O1 CUES- l 16 got 2-fi-acetanilidovinyl-6-methylquinoline methiodidall g. of 1-phenylpyrrocoline. and 100 cc. of glacial acetic acid were mixed and refluxed for 30 minutes. The dye-iodide separated in the hot. The reaction mixture was chilled and the solid filtered off. It was washed with acetone and then with hot water and dried. A yield of g. (65 per cent) of blue green needles 'was obtained whichafter two recrystallizationsfrom methyl a m-2m e converted to the dye-chloride by treating with a' boiling methyl alcoholic solution with vemnprm prepgre'd 'fi'fifnti l g'$ -*6f silver-ultra e-.-"-The silver salts were filtered off and the filtrate concentrated to a small volume on a steam bath. The dye-chloride was precipitated from the residue with diethyl ether in the form of a dull green powder. It was filtered oil and washed with diethyl ether and dried. A yield of 11 g. of dye-chloride of melting point of 251-252 C. with decomposition was obtained which was an 87 per cent yield. Analysis: Cl calc. 8.63; found 8.65. 1

In the same manner described in the above Example 7, (l-methyl-Z-quinoline)(2-methyl-1- pyrrocoline)dimethinecyanine chloride can be prepared from 2-acetanilidovinylquinoline methiodide and z-methyl-l-pyrrocoline; (1-methyl-4- quinoline) (2,3 dimethyl-l-pyrrocoline)dimethinecyanine chloride can be prepared from 4-acetanilidovinylquinoline methiodide and 2,3-dimethyl-l-pyrrocoline; (l-methyl-G-dimethylaminoquinoline) (2 methyl-l-pyrrocoline)dimethinecyanine chloride can be prepared from 2-acetanilidovinyl-6-dimethylaminoquinoline methiodide and 2-methyl-1-pyrrocoline, etc.

The dye-chlorides and dye-toluenesulfonates described above can be converted to the corresponding dye-bromides by treating a hot methyl alcoholic solution of the dye-chloride or dye-toluenesulfonate with a concentrated aqueous solution of potassium bromide. The dye-bromide separates out, upon chilling, if necessary. The dyeiodides can be converted to the corresponding dye-perchlorates by treating a hot methyl alcoholic solution of the dye-iodide with a concentrated aqueous solution of sodium perchlorate. The dye-perchlorate separates out. Dyethiocyanates can be made from dye-iodides by stirring the dye-iodide with a hot methyl alcohol suspension of silver thiocyanate, filtering oil. the silver salts, and isolating the dye-thiocyanate from the methyl alcohol solution.

The herein-described quinoline dimethine dyes are of particular value in the treatment of worm infestations wherethe invading organism is of the class Nematoda (round worms). Among the various species of worms affected by these compounds are hookworms, ascorids, filarids and whipworms. The quinoline dimethine'dyes containing an anion, such as chloride, benzenesulfonate, p-toluenesulfonate, methylsulfate, ethylsulfate, acetate or propionate are the more soluble compounds and the most useful therapeutically.

The instant application is a continuation-inpart of our copending application Serial No. 407,033, filed August 15, 1941, now Patent No. 2,409,612, October 22, 1946, as a division of application Serial No. 317,726, filed February 7, 1940 (now U. S. Patent 2,298,731, dated October 13, 1942).

What we claim as our invention and desire to be secured by Letters Patent of the United States 1. The pyrrocoline polymethinecyanine dyes which are represented by the following general formula:

all)

=ttfiereifi RErpre s ejrits a rimary new rade (:5;-

taining 1 -=to5 carbon atomsfX repre'sent's an anion, Zurepresents the non-metallic atoms necessary to cqmplete a heteroc'yclic} nucleus selected from the group consisting of lbenzoxazole nuclei, benzothiazole nuclei andouinoline nuclei, d represents a positive integer of from 2 to 3, Q represents the non-metallic atoms necessary to compiletea pyridine :nucleus =,fR1 and R2 each represeiits'ai'niember selected from the group consisting of a hydrogen atom, a methyl group and an aryl group of the benzene series.

2'; The pyrrocoline dimethinecyanine dyes which are represented by the following general formula:

wherein R represents a primary alkyl group containing from 1 to 5 carbon atoms, X represents an anion and Z represents the non-metallic atoms necessary to complete a benzoxazole nucleus.

3. The pyrrocoline dimethinecyanine dye which is represented by the following formula:

4. The pyrrocoline dimethinecyanine dyes which are represented by the following general formula: 1

wherein R represents a primary alkyl group containing from 1 to 5 carbon atoms, X represents an anion, and Z represents the non-metallic atoms necessary to complete a benzoxazole nucleus.

5. The pyrrocoline dimethinecyanine dye which is represented by the following formula:

6. The pyrrocoline dimethinecyanine dyes which are represented by the following general formula:

it i N wherein R represents a primary alkyl group containing from 1 to 5 carbon atoms, X represents an anion and Z represents the non-metallic atoms necessary to complete a quinoline nucleus.

The pyrrocollne dimethinecyanine dye qBEFEIQENCES which is represented by the following formula: The IbH6winQ=refrnceS a'r of rebrd in tlib fi'lgofthispateptp 5 T j'I O E N PA ENT CH=CH C Number I Cduntry t {D t 529,440 v Great Britain NOV. 21, 1940 N C \CI CuHa- ==C|JH ROBERT E. SPRAGUE. I I LESLIE G. S. BROOKER; l0 

1. THE PYRROCOLINE POLYMETHINECYANINE DYES WHICH ARE REPRESENTED BY THE FOLLOWING GENERAL FORMULA: 